Effect of circulating small extracellular vesicles isolated from recurrent pregnancy loss (RPL) women and normal pregnant women on decidualization.

INTRODUCTION

Studies have demonstrated a correlation between recurrent pregnancy loss (RPL) and anomalies in the decidualization process. The aim of this study was to explore whether circulating small extracellular vesicles (sEVs) isolated from women with recurrent pregnancy loss modulate decidualization.

METHODS

Circulating sEVs were isolated using precipitation method from pregnant women with RPL history (n = 23) or women with normal pregnancy (n = 20). Nanoparticle tracking analysis, transmission electron microscopy and western blotting were used to characterize the sEVs. Decidualization was induced in human endometrial stromal cell line, THESCs, by addition of estrogen, medroxy progesterone acetate, and 8-Br-cAMP. The effect of sEVs on decidualization was evaluated by observing changes in morphology and measuring the decidual markers such as prolactin (PRL) and insulin-like growth factor binding protein-1 (IGFBP1) at both transcript and protein levels.

RESULTS

THESCs stimulated with decidualization media upregulated the expression of the decidualization markers, PRL and IGFBP1, in a time-dependent manner. Addition of sEVs further increased PRL and IGFBP1. However, no difference was observed in the effect of sEVs isolated from RPL or normal pregnant women. Viability of the THESCs did not alter after incubation with sEVs isolated from any cohort of women.

DISCUSSION: Collectively, our findings suggest that circulating maternal sEVs can modulate the decidualization of THESCs in vitro. However, differential effect of sEVs from different group of women could not be established. Future studies exploring the effect of the molecular cargo of extracellular vesicles on the decidualization process are warranted.